Optimizing Care in Unresectable Stage III NSCLC: Chemoradiation and Immunotherapy

Patients with unresectable stage III lung cancer benefit from concurrent chemoradiation followed by durvalumab maintenance immunotherapy as the current standard of care, though treatment selection requires careful consideration of patient fitness and tumor characteristics. For frail patients or those with significant medical comorbidities, health care providers may opt for sequential therapy approaches where systemic treatment is administered first, followed by radiation therapy without concurrent chemotherapy. This sequential approach reduces acute toxicity while maintaining therapeutic efficacy, particularly when radiation can be delivered using abbreviated fractionation schedules.

Recent clinical trial results demonstrate that adding immunotherapy during concurrent chemoradiation does not improve outcomes compared with the standard approach of postradiation durvalumab maintenance, with multiple phase 3 trials confirming that immunotherapy should be given after rather than during chemoradiation. Patients who are completely ineligible for chemotherapy may still benefit from radiation therapy combined with immunotherapy, as emerging data suggest durvalumab provides benefit even when added to radiation alone. This expanding treatment paradigm offers hope for patients previously considered to have limited therapeutic options due to medical contraindications.

Treatment planning for patients with stage III disease increasingly involves careful consideration of radiation field design and fractionation to minimize toxicity while maximizing the potential for subsequent adjuvant therapies. Health care providers recognize that modern approaches aim to treat visible disease precisely rather than using large prophylactic volumes, reducing the risk of pneumonitis that could delay or prevent initiation of consolidation immunotherapy. Patients benefit from this evolution in radiation planning, which balances local control objectives with the need to preserve patient fitness for extended adjuvant treatment courses that may continue for a year or longer following completion of definitive chemoradiation.